ES2968015T3 - Oral care composition - Google Patents

Abstract

The present invention relates to an oral care composition comprising o-cimen-5-ol, dipotassium glycyrrhizinate, 4-hydroxyacetophenone and water, as well as its use in oral care, in particular for the treatment and/or prevention of dental plaque formation. caries formation, stone formation, halitosis, gingivitis, periodontitis, peri-implant mucositis and/or peri-implantitis. (Automatic translation with Google Translate, without legal value)

Description

DESCRIPTION

Oral care composition

FIELD OF INVENTION

The invention relates to the field of oral care compositions, in particular to mouthwashes, toothpastes and toothpastes comprising o-cymen-5-ol, dipotassium glycyrrhizinate and 4-hydroxyacetophenone.

BACKGROUND OF THE INVENTION

Oral hygiene is the practice of keeping the mouth clean, and is considered to be the best means of preventing cavities (tooth decay), gingivitis, periodontitis, and other dental and oral disorders such as bad breath (halitosis). Oral hygiene is necessary for all people to maintain the health of their teeth and mouth. There are three key stages to regulate dental maintenance and health: brushing, flossing and rinsing with a mouthwash. Brushing your teeth involves using toothpaste along with a toothbrush to help remove food debris and dental plaque. Mouthwashes are used to clean and freshen the mouth and for oral hygiene. Antiseptic and antiplaque compounds are present in mouthwashes and toothpaste to rinse and destroy microorganisms that cause plaque, gingivitis, and bad breath.

Glycyrrhizin compounds have been reported to have anti-inflammatory activity that helps in the prevention of gingivitis and periodontitis [Asl, M. N. et al, Phytother. Res.,2008, 22, 709-724].

It has also been reported that isopropylmethylphenols penetrate deep into the plaque and show a high bactericidal effect [Park, Y.-D.et al., Int. J. Clin. Prev. Dent.,2010, 6(2), 55-61]. In addition, isopropylmethylphenols also reduce breath concentrations of volatile sulfur compounds (VSCs), which are associated with halitosis [Choet a l, Int J Oral Health,2009, 5, 37-47].

Combinations of these components, i.e. glycyrrhizin compounds and isopropylmethylphenols, have been reported to be particularly advantageous. In particular, a study conducted by Choet al. [Int J Oral Health,2009, 5, 37-47] concluded that a mouthwash comprising these components was safe and effective in reducing periodontal pocket depth and gingival crevicular fluid, which are markers of periodontopathy, and also in terms of effective inhibition of oral microorganisms. In a clinical study reported by Parket al. [Int. J. Clin. Prev. Dent.,2010, 6(2), 55-61], the effect of toothpaste containing isopropylmethylphenol and dipotassium glycyrrhizinate in gingival states showed that the combination of these compounds reduced halitosis, plaque index, crevicular fluid gingival, periodontal pocket depth and gingival index. The authors of the report concluded that the combination of isopropylmethylphenol and dipotassium glycyrrhizinate appeared to show a synergistic effect.

Therefore, the use of isopropylmethylphenols and glycyrrhizin compounds in oral care products is highly desirable, particularly to help control the development of dental plaque, tartar formation, halitosis, gingivitis and periodontitis.

For the manufacturing of oral care products, knowledge of fluid rheology is important for process equipment such as pipes, pumps, and mixers, which are commonly used in manufacturing procedures.

According to their rheological behavior, fluids can be classified into Newtonian and non-Newtonian fluids. Newtonian fluids are those that present a linear relationship between shear speed and shear stress. In these fluids, the slope n (viscosity) is constant and, therefore, the viscosity of Newtonian fluids is independent of the shear rate. On the other hand, in non-Newtonian fluids, the viscosity depends on the shear rate. Non-Newtonian fluids can exhibit either shear fluidization or shear thickening behavior and, in some cases, these fluids also exhibit a permanent deformation load, that is, a stress level that must be exceeded before the fluid begins to flow. Most fluid compositions, such as oral care compositions and fluid compositions of intermediates used in their manufacturing processes, exhibit non-Newtonian behavior. Non-Newtonian fluids can be classified as plastic fluids, dilatant fluids and pseudoplastic fluids. In plastic fluids, a critical stress level (permanent deformation load) must be reached to begin flowing. Below this critical stress, <t>, the material behaves like a solid, absorbing stress energy without flowing. Once the critical stress threshold has been reached, the material yields to flow, hence the term, permanent deformation load. In pseudoplastic fluids, the viscosity decreases as the shear rate increases, but these fluids do not have a permanent deformation load, that is, they flow instantaneously after the application of stress. Dilatant fluids have shear thickening properties, that is, the viscosity of the fluid increases as the shear rate increases.

Rheological studies are used to evaluate fluid properties. Flow curve models are used to characterize the shapes of flow behavior. Models describing pseudoplastic behavior include power law model, Carreau, Cross, etc. Models that describe plastic behavior include the Bingham, Herschel-Bulkley and Casson model [Mitsoulis,J. Non-Newtonian Fluid Mech.,2007, 141, 138 147].

In industrial manufacturing processes, pseudoplastic fluids are preferred over plastic fluids because there is no stress level that must be exceeded before the fluid begins to flow. If a permanent deformation load must be overcome, as with plastic fluids, pumps and mixers are negatively affected and pipes may become clogged.

Therefore, there is a need for alternative oral care products that comprise isopropylmethylphenols and glycyrrhizin compounds and that have rheological properties suitable for the manufacturing process, that is, that have pseudoplastic fluid behavior.

SUMMARY OF THE INVENTION

The present inventors have surprisingly found that compositions comprising isopropylmethylphenols such as o-cymen-5-ol, and/or glycyrrhizin compounds, such as dipotassium glycyrrhizinate, do not have desirable rheological properties for manufacturing processes because they behave It has plastic fluids. Unexpectedly, the addition of hydroxyacetophenone to a composition comprising an isopropylmethylphenol and a glycyrrhizin compound modifies the rheological behavior of the composition to that of a pseudoplastic fluid, which is preferred in the process of manufacturing oral care compositions. The compositions of the invention are also advantageous due to their low cytotoxicity, antioxidant effects, anti-inflammatory effects, healing properties, microbiological profiles, cleansing properties, plaque penetration and reduction properties, their properties with respect to their stability, in particular against light, temperature or external forces such as the force of gravity.

Therefore, in a first aspect, the present invention relates to an oral care composition comprising: - 0.005 to 1% by weight of o-cimen-5-ol,

- from 0.005 to 1.5% by weight of dipotassium glycyrrhizinate,

- from 0.05 to 5% by weight of 4-hydroxyacetophenone, and

- at least 15% by weight of water.

In a second aspect, the present invention relates to an oral care composition as defined in the first aspect for use in the treatment and/or prevention of dental plaque formation, caries formation, tartar formation, halitosis, gingivitis, periodontitis, peri-implant mucositis and/or peri-implantitis.

DETAILED DESCRIPTION OF THE INVENTION

Disclosed is an oral care composition according to the claims herein comprising:

- an isopropylmethylphenol compound,

- a glycyrrhizin derivative selected from the group consisting of glycyrrhizinic acid, glycyrrhetinic acid, salts thereof, and mixtures thereof,

- a hydroxyacetophenone, and

- water.

The term “oral care” compositions means that the compositions are intended for topical use in the mouth, so that any component present in the composition needs to be orally acceptable, that is, safe for topical use in the mouth. mouth in the quantities and concentrations provided.

The term "isopropylmethylphenol compound" refers to compounds having a phenyl ring substituted with a hydroxyl group, a methyl group and an isopropyl group, as represented by formula (I).

Examples of isopropylmethylphenol compounds are o-cimen-5-ol (or 4-isopropyl-3-methylphenol of formula Ia), thymol (or 2-isopropyl-5-methylphenol of formula Ib) and 3-isopropyl-5-methylphenol ( of formula Ic), whose structures are represented below.

The oral care compositions described herein may comprise one or more (such as 2 or 3) isopropylmethylphenol compounds, preferably one.

The isopropylmethylphenol compounds may be present in the oral care compositions described herein in a concentration of from 0.005 to 1% by weight with respect to the total weight of the composition, preferably from 0.01 to 0. 5% by weight, more preferably from 0.02 to 0.1% by weight.

In the compositions of the present invention, the isopropylphenylphenol compound is o-cymen-5-ol.

In the compositions of the present invention, o-cimen-5-ol is present in a concentration of from 0.005 to 1% by weight with respect to the total weight of the composition, preferably from 0.01 to 0. 5% by weight, more preferably from 0.02 to 0.1% by weight.

The glycyrrhizin derivative present in the oral care compositions described herein may be selected from the group consisting of glycyrrhizinic acid, glycyrrhetinic acid, salts thereof, and mixtures thereof. These compounds are widely applied as natural sweeteners, and are used in cosmetics and pharmaceutical products. They can be isolated from the roots and stolon of perennial plants of the species Glycyrrhiza, such as Glycyrrhiza glabra.

“Glycyrrhizinic acid” or “glycyrrhizic acid” has the chemical structure depicted below.

Glycyrrhizinic acid has three acid groups that can form salts with a cation, including organic cations (such as ammonium) as well as inorganic cations (such as alkali metals, e.g., sodium and potassium; and alkaline earth metals, e.g., calcium and magnesium. ). The preferred cations for forming salts with glycyrrhizinic acid are potassium, sodium and ammonium. Examples of glycyrrhizinic acid salts are dipotassium glycyrrhizinate, diammonium glycyrrhizinate, disodium glycyrrhizinate, monoammonium glycyrrhizinate, monosodium glycyrrhizinate and monopotassium glycyrrhizinate, preferably dipotassium glycyrrhizinate.

“Glycyrrhetinic acid” or “enoxolone” has the chemical structure depicted below.

Glycyrrhetinic acid has an acidic group that can form salts with a cation, including organic cations (such as ammonium) as well as inorganic cations (such as alkali metals, e.g., sodium and potassium; and alkaline earth metals, e.g., calcium and magnesium. ). The preferred cations for forming salts with glycyrrhetinic acid are potassium, sodium and ammonium. Examples of glycyrrhetinic acid salts are potassium glycyrrhetinate, ammonium glycyrrhetinate, and sodium glycyrrhetinate.

The glycyrrhizin derivative in the oral care compositions described herein may be glycyrrhizinic acid or a salt thereof, more preferably dipotassium glycyrrhizinate.

The glycyrrhizin derivative may be present in the oral care compositions described herein in a concentration of from 0.005 to 1.5% by weight with respect to the total weight of the composition, preferably from 0.01 to 1.5% by weight with respect to the total weight of the composition. 1.5% by weight, more preferably from 0.02 to 1% by weight, more preferably from 0.02 to 0.5% by weight.

In the oral care compositions of the present invention, the glycyrrhizin derivative is dipotassium glycyrrhizinate.

In the oral care compositions of the present invention, dipotassium glycyrrhizinate is present in a concentration of from 0.005 to 1.5% by weight with respect to the total weight of the composition, preferably from 0.01 to 1 .5% by weight, more preferably from 0.02 to 1% by weight, more preferably from 0.02 to 0.5% by weight.

The term hydroxyacetophenone refers to a compound of formula (IV).

Examples of hydroxyacetophenones are 2-hydroxyacetophenone, 3-hydroxyacetophenone and 4-hydroxyacetophenone.

The oral care compositions described herein may comprise one or more (such as 2 or 3) hydroxyacetophenones, preferably one.

Hydroxyacetophenone may be present in the oral care compositions described herein in a concentration of from 0.05 to 5% by weight with respect to the total weight of the composition, preferably from 0.05 to 1, 5% by weight, more preferably from 0.05 to 1% by weight, even more preferably from 0.1 to 1% by weight.

In the oral care compositions of the present invention, the hydroxyacetophenone is 4-hydroxyacetophenone.

In the oral care compositions of the present invention, 4-hydroxyacetophenone is present in a concentration of from 0.05 to 5% by weight with respect to the total weight of the composition, preferably from 0.05 to 1, 5% by weight, more preferably from 0.05 to 1% by weight, even more preferably from 0.1 to 1% by weight.

Therefore, the oral compositions according to the present invention comprise:

- from 0.005 to 1% by weight of o-cimen-5-ol,

- from 0.005 to 1.5% by weight of dipotassium glycyrrhizinate,

- from 0.05 to 5% by weight of 4-hydroxyacetophenone, and

- at least 15% water,

in which the % by weight are expressed with respect to the total weight of the composition.

In the oral care compositions described herein, the weight ratio of hydroxyacetophenone to glycyrrhizin derivative is from 15:1 to 0.5:1, preferably from 15:1 to 1:1, more preferably from 10:1 to about 1:1, even more preferably about 1:1.

In the oral care compositions described herein, the weight ratio of hydroxyacetophenone to isopropylmethylphenol compound is from 10:1 to 0.5:1, preferably from 10:1 to 1:1, more preferably from 5:1 to about 1:1, even more preferably about 1:1.

Therefore, in a preferred embodiment of the oral care compositions according to the present invention, the weight ratio of 4-hydroxyacetophenone to dipotassium glycyrrhizinate is from 15:1 to 0.5:1, preferably from 15:1 up to 1:1, more preferably from 10:1 to about 1:1, even more preferably about 1:1.

Therefore, in another preferred embodiment of the oral care compositions according to the present invention, the weight ratio of 4-hydroxyacetophenone to o-cymen-5-ol is from 10:1 to 0.5:1, preferably from 10:1 to 1:1, more preferably from 5:1 to about 1:1, even more preferably about 1:1.

The oral care compositions described herein, particularly those of the present invention, also comprise water. Preferably, the water is present in an amount of at least 15% by weight, at least 20% by weight, at least 25% by weight, at least 30% by weight, at least 40% by weight, at least 50% by weight, at least 60% by weight, at least 70% by weight, at least 75% by weight, or at least 80% by weight, in which the % by weight is expressed with respect to the total weight of the composition.

Preferably, the oral care compositions described herein, in particular those of the present invention, also comprise one or more components selected from the group consisting of fluoride ion sources, surfactants, cosolvents, humectants, sweeteners, binders, mouthfeel, abrasives, desensitizing agents, other oral care active ingredients, pH modifying agents, chelating agents, preservatives, flavoring and coloring agents.

Sources of fluoride ions include sodium fluoride, potassium fluoride, stannous fluoride, potassium monofluorophosphate, sodium monofluorophosphate, ammonium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride such as (N,N,N'- tris(2-ethanol)-N'-octadecyltrimethyldiamine dihydrofluoride), ammonium fluoride, and combinations thereof. Preferably, the oral care compositions described herein, particularly those of the present invention, may also contain a fluoride ion source or fluoride-providing component in amounts sufficient to supply 50 to 5000 ppm fluoride ion, e.g. , from 100 to 1000 ppm of fluoride ion. Sources of fluoride ions may be added to the compositions described herein, in particular those of the present invention, at a level in the range of 0.001% by weight to 10% by weight, for example, from 0.003% by weight up to 5% by weight, or from 0.01% by weight to 1.2% by weight, in which the % by weight is expressed with respect to the total weight of the composition. However, it should be understood that the weights of the fluoride salts to provide the appropriate level of fluoride ion will obviously vary based on the weight of the counterion in the salt, and such quantities can be readily determined by one skilled in the art. Preferred sources of fluoride ions are sodium fluoride and sodium monofluorophosphate.

The oral care compositions described herein, particularly those of the present invention, may optionally comprise a surfactant. The term “surfactant” refers to compounds that can reduce surface tension. Suitable surfactants include nonionic, anionic, cationic and amphoteric surfactants. Any orally acceptable surfactant may be used.

Examples of nonionic surfactants are block copolymers such as ethylene oxide and propylene oxide block copolymers (e.g., poloxamers), ethoxylated and hydrogenated castor oils, polyoxyethylene sorbitan esters (e.g., polysorbates), fatty alcohol ethoxylates. , alkylphenol ethoxylates, tertiary amine oxides, tertiary phosphine oxides, dialkyl sulfoxides and the like. In a particular embodiment, the nonionic surfactant is selected from ethylene oxide and propylene oxide block copolymers (e.g., poloxamers), ethoxylated and hydrogenated castor oils, and mixtures thereof; preferably poloxamer 407, PEG 40 hydrogenated castor oil and mixtures thereof.

Examples of anionic surfactants are alkyl and alkenyl sulfates and their alkyl ether derivatives, sarcosinates, isethionates and taurates, such as sodium lauryl sulfate, sodium sulfonate of coconut monoglycerides, sodium lauryl sarcosinate, sodium lauryl sethionate, sodium lauryl ether carboxylate, salts. of (Cs-20 alkyl)-sulfate (such as sodium (C14-C16 alkyl)-sulfates), salts of (Cs-20 alkenyl)-sulfates (such as sodium (C14-C16 alkenyl)-sulfates), and sodium dodecylbenzenesulfonate; preferably sodium laurylsarcosinate and sodium salts of (Cs-20 alkyl)-sulfates (such as (sodium Ci4-Ci6 alkyl)-sulfates) and sodium salts of (C8-20 alkenyl)-sulfates (such as (C14 alkenyl -Ci6)-sodium sulfates).

Examples of cationic surfactants are lauryltrimethylammonium chloride, cetylpyridinium chloride, cetyltrimethylammonium bromide, diisobutylphenoxyethyldimethylbenzylammonium chloride, coconut alkyltrimethylammonium nitrite, cetylpyridinium fluoride and mixtures thereof.

Examples of amphoteric surfactants are myristylbetaine, palmitylbetaine, laurylbetaine, cetylbetaine, stearylbetaine, lauramidopropylbetaine, cocoamidoethylbetaine, cocoamidopropylbetaine and the like; preferably cocamidopropylbetaine.

Preferred surfactants include polyoxyethylene hydrogenated castor oils, poloxamers (polypropylene glycol-polyethylene glycol block copolymers), (C8-20 alkyl)-sulfate salts, (C8-20 alkenyl)-sulfate salts, sodium laurylsarcosinate and cocoamidopropylbetaine.

One or more surfactants are optionally present in a total amount in the range of from 1% by weight to 70% by weight, wherein % by weight is expressed with respect to the total weight of the composition.

In addition to water, the oral care compositions described herein, particularly those of the present invention, may comprise one or more cosolvents such as glycerin, propylene glycol and/or ethanol. One or more cosolvents are optionally present in a total amount in the range of from 5% by weight to 20% by weight, where the % by weight is expressed with respect to the total weight of the composition.

The oral care compositions described herein, particularly those of the present invention, may optionally comprise a humectant, which is a substance that maintains and retains moisture. Any orally acceptable humectant may be used, such as sugar alcohols, for example, sorbitol and, and low molecular weight PEG, such as PEG40. Most humectants also function as sweeteners. One or more humectants are optionally present in a total amount in the range of from 1% by weight to 70% by weight, where the % by weight is expressed with respect to the total weight of the composition.

In addition to the humectants described above and the glycyrrhizin derivatives described above (which are essential components of the invention), which also function as sweeteners (i.e., substances that can provide a sweet taste), the oral care compositions described in the This document, particularly those of the present invention, may optionally comprise a sweetener that is not a humectant. Examples of this type of sweeteners include artificial sweeteners such as sucralose, saccharin, acesulfame, neotame, neohesperidin, cyclamate, thaumatin, stevioside. These sweeteners (which are neither humectants nor glycyrrhizin derivatives) may be present in amounts ranging from 0.001% by weight to 2% by weight, where the % by weight is expressed with respect to the total weight of the composition.

The oral care compositions described herein, particularly those of the present invention, may contain a binder, which provides cohesion to the composition. Any conventional binder can be used, such as carboxyvinyl polymers, carrageenans, starches, cellulosic polymers, for example, hydroxyethyl cellulose. carboxymethylcellulose (carmellose), hydroxypropylmethylcellulose and salts thereof (for example, carmellose sodium), natural gums such as xanthan gum, karaya, gum arabic and tragacanth and chitosan. One or more binders may be present in a total amount in the range of 0.1% by weight to 1.5% by weight, where the % by weight is expressed with respect to the total weight of the composition. Preferably, the oral care compositions described herein, in particular those of the present invention, comprise xanthan gum, preferably in an amount in the range of 0.1% by weight to 1.5% by weight, wherein % by weight is expressed with respect to the total weight of the composition.

Mouthfeel agents that may be present in the oral care compositions described herein, particularly those of the present invention, and which relate to materials that confer a desirable texture or other sensation during use of the composition. Such agents include bicarbonate salts, which can impart a clean feeling to teeth and gums due to effervescence and the release of carbon dioxide. Any orally acceptable bicarbonate may be used, such as alkali metal bicarbonates, for example, sodium and potassium bicarbonates, ammonium bicarbonate, and mixtures thereof. One or more bicarbonate salts are optionally present in a total amount in the range of 0.1% by weight to 5% by weight, where the % by weight is expressed with respect to the total weight of the composition.

The oral care compositions described herein, particularly those of the present invention, may also include an abrasive, which removes material from the surfaces of teeth and gums and assists in the mechanical cleaning of teeth. The abrasive may be a silica abrasive such as silica, sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, dicalcium phosphate dihydrate, aluminum silicate, calcined alumina, bentonite or other siliceous materials, sodium chloride, or combinations thereof. themselves. One or more abrasives may be present in a total amount in the range of from 10% by weight to 30% by weight, preferably from 15% by weight to 20% by weight%, in which % by weight It is expressed with respect to the total weight of the composition.

The oral care compositions described herein, particularly those of the present invention, may also comprise desensitizing agents, which may treat hypersensitivity by blocking dentinal tubules when applied to a tooth. Examples of desensitizing agents are potassium salts such as potassium nitrate, potassium chloride, potassium bicarbonate, potassium citrate and potassium oxalate. Such agents can be added in effective amounts, for example, in a total amount usually in the range of from 0.01% by weight to 5% by weight, where the % by weight is expressed with respect to the total weight of the composition.

In addition to the oral care active ingredients mentioned above (such as isopropylmethylphenols, glycyrrhizin derivatives, fluoride ion sources and desensitizing agents), other oral care active ingredients may be present in the compositions described herein, in particular those of the present invention. Such oral care active ingredients can exert any beneficial effects to the teeth and gums, such as reducing tooth hypersensitivity, reducing plaque accumulation, reducing or inhibiting demineralization and promoting remineralization of teeth, inhibiting the formation of microbial biofilm in the oral cavity, reduce or inhibit gingivitis, promote the healing of sores, reduce the levels of acid-producing bacteria, increase the relative levels of non-cariogenic and/or non-plaque-forming bacteria, reduce or inhibit the formation of dental caries, reduce, repair or inhibit previous lesions of enamel decay, treat, alleviate or reduce xerostomia, clean the teeth and oral cavity, reduce erosion, whiten teeth and reduce tartar accumulation. Examples of such agents include alkali metal gluconate salts such as sodium gluconate, panthenol, vitamin E or a derivative thereof such as vitamin E acetate, α-bisabolol, malic acid, calcium glycerophosphate, etc. It should be understood that the weights of these active ingredients may vary depending on the particular active ingredient, and such amounts can be readily determined by one skilled in the art. Typically each oral care active ingredient is optionally present in an amount in the range of from 0.001% by weight to 1% by weight%, where the % by weight is expressed with respect to the total weight of the composition.

The oral care compositions described herein, particularly those of the present invention, may comprise a pH modifying agent, which is a compound that adjusts and/or maintains pH. Such agents include acidifying agents to lower the pH, basifying agents to raise the pH, and buffering agents to control the pH within a desired range. For example, one or more compounds selected from acidifying, basifying and buffering agents may be included to provide a pH of 4.5 to 10.5, preferably 5.5 to 8.5. Any orally acceptable pH modifying agent may be used, including carboxylic, phosphoric and sulfonic acids and their salts (for example, monopotassium phosphate, dipotassium phosphate, monosodium phosphate, trisodium phosphate, citric acid, monosodium citrate, disodium citrate, monosodium malate, etc.), alkali metal hydroxides such as sodium hydroxide, carbonates such as sodium carbonate, bicarbonates, sesquicarbonates, borates, silicates, imidazole and the like. One or more pH modifying agents are optionally present in a total amount effective to maintain the composition in an orally acceptable pH range.

The oral care compositions described herein, particularly those of the present invention, may optionally comprise a chelating agent, which forms complexes with metal ions, such as calcium, magnesium and iron. Examples of chelating agents are citric acid, succinic acid, gluconic acid, etidronic acid, galactaric acid, galacturonic acid, glucuronic acid, phytic acid, ethylenediaminetetraacetic acid (EDTA), methylglycine-W,W-diacetic acid (MGDA), W acid, W-dicarboxymethylglutamic acid (GLDA), and the respective ammonium, sodium and potassium salts; poly(acrylic acids), polymers thereof and the respective ammonium, sodium and potassium salts; and phosphoric acids and polyphosphoric acids and the respective ammonium, sodium and potassium salts. Preferably, the chelating agent is EDTA or an ammonium, sodium or potassium salt thereof. One or more chelating agents are optionally present in a total amount in the range of from 0.1 to 5% by weight, where the % by weight is expressed with respect to the total weight of the composition.

Preservatives may also be present in the oral care compositions described herein, particularly those of the present invention. Preservatives inhibit the development of microorganisms in the oral care composition. Examples of suitable preservatives are chlorhexidine, triclosan, quaternary ammonium compounds (such as benzalkonium chloride) or parabens (such as methyl or propylparaben). One or more preservatives are optionally present in a total amount usually in the range of from 0.001% by weight to 0.5% by weight, where the % by weight is expressed with respect to the total weight of the composition.

The oral care compositions described herein, particularly those of the present invention, may optionally comprise a flavoring agent that is added to modify the taste and aroma of the oral care compositions. Flavoring agents that can be used in the compositions described herein, particularly those of the present invention, include essential oils as well as various aldehydes, asters, alcohols and similar flavoring materials. Examples of essential oils include peppermint, peppermint, anise, wintergreen, sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, lime, grapefruit, and orange oils. Compounds such as menthol, carvone, anethole and vanillin are also useful. Of these, the most commonly used are peppermint and peppermint oils. One or more flavoring agents may be present in the oral care composition in a total concentration in the range of 0.01% by weight to 5% by weight, in which the % by weight is expressed with respect to the total weight of the composition.

The oral care compositions described herein, particularly those of the present invention, may comprise at least one colorant, which is added to modify the color of the compositions. Colorants herein include pigments, dyes, lacquers and agents that impart a particular luster or reflectivity such as pearlescent agents. Any orally acceptable dye may be used, such as titanium dioxide. One or more colorants are optionally present in a total amount in the range of from 0.0001% by weight to 5% by weight, where the % by weight is expressed with respect to the total weight of the composition.

The oral care compositions described herein, particularly those of the present invention, may be in the form of a mouthwash, toothpaste or toothpaste gel.

In the context of the present invention, "mouthwash" is equivalent to "mouthwash", "mouthwash" and "oral solution" and designates liquid compositions that are suitable for oral hygiene, such as reducing the microbial load in the mouth. oral cavity, in particular the bacterial plaque that causes cavities, gingivitis and bad breath. When such compositions are used, they are normally held in the mouth passively and/or agitated through the teeth by contraction of the perioral muscles and/or movement of the head, and may be gargled, and finally spit out.

In the context of the present disclosure, the term “toothpaste” refers to a semi-solid preparation suitable for cleaning teeth when used with a toothbrush. In the context of the present invention, the term "toothpaste gel" refers to a gel preparation suitable for cleaning teeth when used with a toothbrush. Toothpaste gels are similar to toothpaste, but with a more transparent or translucent appearance. In particular, toothpaste gels do not comprise titanium dioxide while toothpastes comprise titanium dioxide.

Preferably, the oral care composition described herein, in particular that of the present invention, is a mouthwash and comprises water in an amount of at least 70% by weight, at least 75% by weight, or at least 80% by weight; preferably at least 75% by weight of water. The % by weight is expressed with respect to the total weight of the composition.

Preferably, the oral care composition described herein, in particular that of the present invention, is a toothpaste gel or toothpaste and comprises water in an amount of at least 15% by weight, at least 20% by weight. weight, at least 25% by weight, at least 30% by weight; preferably at least 10% by weight of water. The % by weight is expressed with respect to the total weight of the composition.

Preferably, the oral care composition described herein, in particular that of the present invention, is a toothpaste gel or toothpaste and comprises water in an amount of from 15% by weight to 35% by weight, from 20% by weight to 35% by weight, from 25% by weight to 35% by weight, from 30% by weight to 35% by weight; preferably from 10% by weight to 35% by weight of water. The % by weight is expressed with respect to the total weight of the composition.

In particular, the oral care composition described herein is in the form of a mouthwash and comprises:

- from 0.01 to 1.5% by weight of a hydroxyacetophenone,

- from 0.005 to 1% by weight of an isopropylmethylphenol compound,

- from 0.005 to 1.5% by weight of a glycyrrhizin derivative selected from the group consisting of glycyrrhizinic acid, glycyrrhetinic acid, salts thereof, and mixtures thereof,

- at least 70% by weight of water,

- optionally 5 to 10% by weight of propylene glycol,

- optionally from 1 to 10% by weight of glycerin, and

- optionally from 1 to 5% by weight of castor oil hydrogenated with PEG40,

in which the % by weight is expressed with respect to the total weight of the composition.

In a preferred embodiment, the oral care composition of the invention is in the form of a mouthwash and comprises: - 0.05 to 1.5% by weight of 4-hydroxyacetophenone,

- from 0.005 to 1% by weight of o-cimen-5-ol,

- from 0.005 to 1.5% by weight of dipotassium glycyrrhizinate,

- at least 70% by weight of water,

- optionally 5 to 10% by weight of propylene glycol,

- optionally from 1 to 10% by weight of glycerin, and

- optionally from 1 to 5% by weight of castor oil hydrogenated with PEG40,

in which the % by weight is expressed with respect to the total weight of the composition.

In one particular, the oral care composition described herein is in the form of a toothpaste gel or toothpaste, preferably toothpaste gel, and comprises:

- from 0.01 to 1.5% by weight of a hydroxyacetophenone,

- from 0.005 to 1% by weight of an isopropylmethylphenol compound,

- from 0.005 to 1.5% by weight of a glycyrrhizin derivative selected from the group consisting of glycyrrhizinic acid, glycyrrhetinic acid, salts thereof, and mixtures thereof,

- from 15 to 35% by weight of water,

- from 30 to 55% by weight of sorbitol,

- optionally from 0.1 to 1.5% by weight xanthan gum,

- optionally from 0.5 to 10% by weight of propylene glycol, and

- optionally from 1 to 15% by weight of glycerin,

in which the % by weight is expressed with respect to the total weight of the composition.

In a preferred embodiment, the oral care composition of the invention is in the form of a toothpaste gel or toothpaste, preferably toothpaste gel, and comprises:

- from 0.05 to 1.5% by weight of 4-hydroxyacetophenone,

- from 0.005 to 1% by weight of o-cimen-5-ol,

- from 0.005 to 1.5% by weight of dipotassium glycyrrhizinate,

- from 15 to 35% by weight of water,

- from 30 to 55% by weight of sorbitol,

- optionally from 0.1 to 1.5% by weight xanthan gum,

- optionally from 0.5 to 10% by weight of propylene glycol, and

- optionally from 1 to 15% by weight of glycerin,

in which the % by weight is expressed with respect to the total weight of the composition.

In a particular embodiment, the oral care composition of the invention is in the form of a toothpaste gel and comprises:

- from 0.05 to 1.5% by weight of 4-hydroxyacetophenone,

- from 0.005 to 1% by weight of o-cimen-5-ol,

- from 0.005 to 1.5% by weight of dipotassium glycyrrhizinate,

- from 15 to 35% by weight of water,

- from 30 to 55% by weight of sorbitol,

- optionally from 0.1 to 1.5% by weight xanthan gum,

- optionally from 0.5 to 10% by weight of propylene glycol, and

- optionally from 1 to 15% by weight of glycerin,

in which the % by weight is expressed with respect to the total weight of the composition.

In another particular embodiment, the oral care composition of the invention is in the form of toothpaste and comprises:

- from 0.05 to 1.5% by weight of 4-hydroxyacetophenone,

- from 0.005 to 1% by weight of o-cimen-5-ol,

- from 0.005 to 1.5% by weight of dipotassium glycyrrhizinate,

- 15 to 25% by weight of water,

- 30 to 40% by weight of sorbitol,

- from 0.1 to 1.5% by weight of xanthan gum,

- optionally from 0.5 to 5% by weight of propylene glycol, and

- optionally 10 to 15% by weight of glycerin,

in which the % by weight is expressed with respect to the total weight of the composition.

The oral care compositions of the invention can be obtained by mixing the components mentioned above.

Uses of compositions

As explained in the background section, isopropylmethylphenols and/or glycyrrhizin compounds have anti-inflammatory activity that helps in the prevention of gingivitis and periodontitis [Asl, M. N. et al, Phytother. Res.,2008, 22, 709-724], have a high bactericidal effect [Park, Y.-D.et al., Int. J. Clin. Prev. Dent.,2010, 6(2), 55-61], and reduce breath concentrations of volatile sulfur compounds (VSCs), which are associated with halitosis [Choet al., Int J Oral Health,2009 , 5, 37-47]. It has also been reported that combinations of these compounds [Parket al., Int. J. Clin. Prev. Dent.,2010, 6(2), 55-61] reduce halitosis, plaque index, gingival crevicular fluid, periodontal pocket depth and gingival index.

Accordingly, the oral care compositions described herein are for use in maintaining the health of the oral cavity, in particular for use in the treatment and/or prevention of the formation of dental plaque, formation of cavities, tartar formation, halitosis, gingivitis, periodontitis, peri-implant mucositis and/or peri-implantitis. Also disclosed herein is the use of an oral care composition as described herein for the manufacture of a medicament for treating and/or preventing the formation of dental plaque, caries formation, tartar formation , halitosis, gingivitis, periodontitis, peri-implant mucositis and/or peri-implantitis. In addition, a method is also disclosed for the treatment and/or prevention of dental plaque formation, caries formation, tartar formation, halitosis, gingivitis, periodontitis, peri-implant mucositis and/or peri-implantitis that comprises contacting a surface of the oral cavity with the oral care compositions as described herein.

Therefore, a second aspect of the present invention relates to the oral care compositions of the invention for use in the maintenance of the oral cavity, in particular for use in the treatment and/or prevention of plaque formation. dental, caries formation, tartar formation, halitosis, gingivitis, periodontitis, peri-implant mucositis and/or peri-implantitis.

This aspect can also be formulated as the use of an oral care composition of the invention for the manufacture of a medicament for treating and/or preventing the formation of dental plaque, caries formation, tartar formation, halitosis, gingivitis, periodontitis, mucositis peri-implant and/or peri-implantitis.

Alternatively, this aspect may be formulated as a method for the treatment and/or prevention of dental plaque formation, caries formation, tartar formation, halitosis, gingivitis, periodontitis, peri-implant mucositis and/or peri-implantitis comprising contacting a surface of the oral cavity with the oral care compositions of the invention.

Alternatively, this aspect may be formulated as the use of the oral care compositions of the invention for the treatment and/or prevention of dental plaque formation, caries formation, tartar formation, halitosis, gingivitis, periodontitis, peri-implant mucositis and/ or peri-implantitis.

For the above purposes, the aqueous oral compositions described herein, particularly those of the present invention, may be contacted with a surface of the oral cavity. Said surface of the oral cavity can be selected from the group consisting of one or more teeth, gum surfaces, tongue surface and combinations thereof. To carry out said contact, when the oral care composition of the invention is a mouthwash, it is normally kept in the oral cavity passively or rinsed around the mouth by contraction of the perioral muscles and/or movement of the head, and may gargle, and finally spit it out. In the case of mouthwashes, the amount of composition dosed into the oral cavity to perform the activity is normally from 2-30 ml, preferably from 5-20 ml and most preferably from 10-15 ml. Contacting may be performed for any suitable amount of time such as for less than thirty seconds, for thirty seconds or more, for about thirty seconds, for about forty seconds, for about one minute or more. To make contact with a surface of the oral cavity, when the oral care composition of the invention is a toothpaste gel or toothpaste, it is normally applied with a toothbrush and mechanical cleaning of the teeth and/or the tongue, preferably for at least two minutes, more preferably for at least three minutes. In the case of toothpaste gels and toothpastes, the amount of composition dosed to carry out the activity is normally from 0.3-4.0 g, preferably from 0.5-2.5 g. Contacting may be carried out at least once a day, preferably at least twice a day, more preferably at least three times a day, such as 1, 2, 3 or 4 times a day. The oral cavity may belong to a human or animal, preferably a human.

The term "treatment", "treating" or "treating", as used herein, refers to means that reverse, alleviate, inhibit the progression of the disease or disorder these terms refer to, or one or more symptoms of such disease or condition.

The term "prevention", "preventing" or "prevent", as used herein, refers to preventing the occurrence of a particular disease or disorder. Prevention may be complete (for example, the complete absence of a disease or disorder). Prevention may also be partial, so that, for example, the occurrence of a disease or disorder in a subject is less than would have occurred without administration of the oral care composition of the present invention. Prevention also includes reducing the risk of developing the disease or disorder. In a particular embodiment, the compositions of the invention are for use in prevention.

The term “dental plaque” refers to a thin film that is made up of food debris, bacteria, and saliva. If dental plaque is not removed regularly, it adheres to the surface of the enamel, attacking the structures of the teeth and producing a series of substances that cause swelling of the gums, leading to gingivitis (inflammation of the gum), redness and probable gingival bleeding.

The term “tartar” or “tartar” refers to a form of hardened dental plaque. It is produced by the precipitation of minerals from saliva and gingival crevicular fluid into plaque on the teeth. This precipitation process destroys the bacterial cells within dental plaque, but the rough, hardened surface that forms provides an ideal surface for further plaque formation. This leads to tartar buildup, which compromises the health of the gingiva (gum). Tartar can form both along the gingival line, where it is called supragingival, and within the narrow groove between the teeth and the gingiva, where it is called subgingival.

The term “gingivitis” refers to an inflammation of the gums that results in increased sensitivity and irritation and is often accompanied by bleeding. Its most common trigger is dental plaque or biofilm, which consists of a thin film of food debris, bacteria and saliva. If not treated in time, it can progress to periodontitis (pyorrhea), and even enters the tooth and damages its bone structure, leading to irreversible tooth loss.

The term “periodontitis” refers to an inflammatory gingival process that extends to the periodontal ligament that holds and fixes the tooth, and even to the alveolar bone, destroying both tissues. Periodontal pockets appear, which are an increase in the gap or space between the surface of the tooth and the inner part of the gum. This destructive process extends until the stability of the tooth is compromised. Due to the loss of fixation, in the final stages the teeth separate and become loose, losing their normal location, and finally the tooth falls out irremediably. It has been found that Streptococci, spirochetes and Bacteroides are the possible pathogens responsible for the disease [Prasanth M., Dent Res J (Isfahan), 2011, 8(2), 85-94; Menendez A.et al., Oral Microbiology Immunology,2005, 20(1), 31-34].

The term “halitosis” or “bad breath” refers to the presence of unpleasant odors that can be detected in the exhaled air. Halitosis is a condition that affects many people. There are multiple types of halitosis and they are classified depending on the source or cause of this bad breath: physiological halitosis, pathological halitosis (oral cause, 87% of all halitosis, and extraoral cause), pseudohalitosis and halitophobia. Therefore, bad breath due to an oral cause is the most common. This type of halitosis is caused by the production and release of volatile compounds, mainly sulfur. Other molecules such as diamines (e.g. cadaverine) are also linked to halitosis. Volatile sulfur compounds are caused by bacteria that grow in the mouth in conditions without oxygen (anaerobic). These volatile sulfur compounds come from the metabolism of food bacteria or remain trapped in the mouth.

The term “cavities” refers to the degradation of teeth due to acids produced by bacteria. Streptococcus mutans is considered one of the main bacteria involved in this process. Furthermore, other microflora such as Candida are also associated with active caries lesions [Prasanth M.,Dent Res J (Isfahan),2011, 8(2), 85-94]. Cavities can be several different colors from yellow to black. Symptoms may include pain and difficulty eating. Complications can include inflammation of the tissue surrounding the tooth, tooth loss, and infection or abscess formation. It is a disease characterized by a series of reactions that lead to the hard tissues of the teeth to soften, and if left untreated, advances from the surface to the interior, eventually leading to irreversible destruction of the tooth. Normally, cavities go unnoticed by the patient. A detailed examination will detect white cast-like discolorations or spots (areas where there is no enamel) or brown pigmentation on the surface of the tooth. This phase can be characterized by a certain sensitivity (strange sensation) to some foods, particularly sweet or hot or cold drinks, although usually there is no real pain. When decay progresses and affects the pulp or nerve inside the tooth, pain will usually ensue, although if the condition is very slow it can destroy a large part of the nerve without pain. When the condition is deep, abscesses (better known as phlegmons, that is, destroyed dental material and pus) can form and lead to great inflammation and pain.

The term “peri-implant mucositis” refers to an inflammatory lesion of the soft tissues surrounding an endosseous implant in the absence of loss of supporting bone or continued loss of marginal bone. Peri-implant mucositis is caused by bacteria from dental biofilms, which disrupt the homeostasis of host microbes at the implant-mucosa interface, resulting in an inflammatory lesion. Biofilm removal is a prerequisite for the prevention and treatment of peri-implant mucositis. Peri-implant mucositis is considered a precursor to peri-implantitis.

The term “peri-implantitis” refers to an inflammatory lesion of the mucosa that affects the tissue surrounding the implant, predominantly the supporting bone with loss of osseointegration. Like peri-implant mucositis, it is also caused by the adhesion of pathogenic bacterial biofilms on the implant surface and peri-implant tissues.

In the context of the invention, the term "approximately" when characterizing a value refers to ±10% of said value, preferably ±5% of said value.

Preferably, the term "one or more" refers to 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, more preferably to 1, 2, 3, 4 or 5, even more preferably to 1 , 2 or 3.

The following examples are provided to illustrate the invention but should not be considered to limit its scope.

Examples

Compositions

Oral care compositions (450 g) were prepared by mixing the components disclosed in the table below. The components and their quantities (expressed as % w/w, i.e. % by weight) of each composition are provided in the tables below.

The tables below disclose specific formulations of mouthwash, toothpaste and toothpaste gel. E m l f rm l i n l ri:

Eem the formulation of mouthwash 7:

E m l f rm l i n nífri:

E m l f rm l i n l nífri:

The binder is preferably xanthan gum.

rheological studies

Flow curves representing the change in shear stress (<t>in Pa) and viscosity (n in Pas) versus shear rate (y in s-1) for the compositions of Comparative Examples 1- 3 and for example 4 have been obtained in a rheometer (HAAKE MARS) by subjecting the compositions to the following conditions: shear speed from 0 to 100 s-1 in 3 min, 1 min at a shear speed of 100 s-1 , and cutting speed from 100 to 0 s-1 in 3 min. The permanent deformation load (<to>) corresponds to the first values measured by the device when the cutting speed is increased from 0 to 100 s-1 in 3 min. All rheological studies were carried out at a temperature of 20°C. The experiments were carried out by applying 2 g of the test formulation to the sample area of the rheometer and then lowering the movable part of the rheometer over the sample area, removing the excess formulation.

The flow curves obtained were fitted to the Herschel-Bulkley model according to equation 1 (which describes plastic fluid behavior) and to the Cross model according to equation 2 (which describes pseudoplastic fluid behavior) [Alderman N. (1997 ), “Non-Newtonian Fluids: Guide to Classification and Characteristics”, ESDU data element 97034].

Herschel-Bulkley model:

r = r 0K fn (Equation 1)

in which

tes the shear stress (in Pa),

toes the permanent deformation load (in Pa),

Kes a coefficient (in P asn),

Yes the cutting speed (in s-1), and

nes the exponent.

Cross model:

Vo-y™

V = y™1(ky)n

in which

nes the dynamic viscosity (in Pa s),

no is the asymptotic value of the viscosity at a very low shear rate (in Pa s),

is the asymptotic value of the viscosity at a very high shear rate (in Pa s),

k is a coefficient (in sn),

yes the cutting speed (in s-1), and

nes the exponent.

The correlation coefficient (r) of the fit and the corresponding parameters of the equations were calculated. The model that had the highest correlation coefficient was selected.

L r l r n n n l l nin in:

These results collected in the previous table show that the compositions of comparative examples 1-3 fit very well to the Herschel-Bulkley model, that is, these compositions have a plastic fluid behavior, while the composition of example 4 fits very well to the Cross model, that is, it has pseudoplastic behavior.

The permanent deformation load for the compositions was determined to verify the previous results. The experimental values obtained r r i n n n l l n in i n:

These results confirm that the composition of example 4 has a pseudoplastic behavior since it has no permanent deformation load (to= 0 Pa), while the compositions of comparative examples 1-4 have permanent deformation load values in the range of 3.1-3.3 Pa.

Microbiological studies

Antimicrobial activity studies were carried out against Streptococcus mutans (ATCC 25175) and Candida albicans (ATCC 90028) with the compositions of example 4. The control was a composition comprising 2% by weight of castor oil hydrogenated with PEG 40, 7 % by weight of propylene glycol and water (c.s.p. 100% by weight). The culture media and incubation conditions for each microorganism are provided in the table below:

Determination of maximum inhibitory dilution (MID):

Various dilutions of the compositions under study were incubated with the microorganisms (104 cfu/ml) grown in microtiter plates in the corresponding culture media and incubation conditions. The DIM was defined as the highest dilution (i.e., the lowest concentration) that can completely inhibit visible microbial growth. [Guidelines from EUCAST (European Committee on Antimicrobial Susceptibility Testing) and CLSI (Clinical and Laboratory Standards Institute)]

Determination of the maximum bactericidal dilution (MBD):

20 μl of the dilutions of the test compositions from the DIM experiment described above in which no visible growth of microorganisms had been observed in the DIM test were plated on a solid agar medium. The seeded plates were incubated under the conditions described in the previous table. The DBM corresponded to the highest dilution (i.e., the lowest concentration) capable of completely inhibiting microbacterial growth. Determination of bacterial death kinetics:

The kinetics of bacterial death of the compositions under study were determined by bringing the bacterial suspensions into contact at a concentration of from 5x105 to 2x106 cfu/ml. After 1, 2 and 5 minutes, a sample (100 μl) was extracted and diluted 100 times. The number of viable cells was determined by plating on solid agar medium. The plates were incubated under the corresponding conditions given in the table above and the number of bacteria was determined.

The DIM and DBM results are provided in the table below, expressed as the dilution of the subject composition.

The composition of example 4 showed antibacterial activity against S.mutansyC. albicans.

The composition of Example 4 was further tested for its bacterial killing kinetics against C. albicans.Results are provided in the table below as bacterial counts (cfu/ml) and % survival in parentheses.

________ ________

The composition of example 4 showed bacteriostatic activity against C. albicansy is a fast and active composition against this type of bacteria.

Claims (9)

1. Oral care composition comprising: - from 0.005 to 1% by weight of o-cimen-5-ol, - from 0.005 to 1.5% by weight of dipotassium glycyrrhizinate, - from 0.05 to 5% by weight of 4-hydroxyacetophenone, and - at least 15% by weight of water, in which the weight % are expressed with respect to the total weight of the composition. 2. Oral care composition according to claim 1, wherein water is present in an amount of at least 20% by weight, at least 25% by weight, at least 30% by weight, at least 40% by weight, at least 50% by weight, at least 60% by weight, at least 70% by weight, at least 75% by weight, or at least 80% by weight, in which the % in Weight is expressed with respect to the total weight of the composition. 3. Oral care composition according to any of the preceding claims, further comprising one or more components selected from the group consisting of fluoride ion sources, surfactants, cosolvents, humectants, sweeteners, binders, mouthfeel agents, abrasives, desensitizing agents, other oral care active ingredients, pH modifying agents, preservatives, chelating agents, flavoring and coloring agents. 4. Oral care composition according to any of the preceding claims, in the form of a mouthwash, toothpaste gel or toothpaste. 5. Oral care composition according to any of the preceding claims, in the form of a mouthwash comprising: - from 0.05 to 1.5% by weight of 4-hydroxyacetophenone, - from 0.005 to 1% by weight of o-cimen-5-ol, - from 0.005 to 1.5% by weight of dipotassium glycyrrhizinate, - at least 70% by weight of water, - optionally 5 to 10% by weight of propylene glycol, - optionally from 1 to 10% by weight of glycerin, and - optionally from 1 to 5% by weight of castor oil hydrogenated with PEG40, in which the % by weight is expressed with respect to the total weight of the composition. 6. Oral care composition according to any of claims 1 to 4, in the form of toothpaste gel or toothpaste comprising: - from 0.05 to 1.5% by weight of 4-hydroxyacetophenone, - from 0.005 to 1% by weight of o-cimen-5-ol, - from 0.005 to 1.5% by weight of dipotassium glycyrrhizinate, - from 10 to 35% by weight of water, - from 30 to 55% by weight of sorbitol, - optionally from 0.1 to 1.5% by weight xanthan gum, - optionally from 0.5 to 10% by weight of propylene glycol, and - optionally from 1 to 15% by weight of glycerin, in which the % by weight is expressed with respect to the total weight of the composition. 7. Oral care composition according to any of the preceding claims, wherein the weight ratio of 4-hydroxyacetophenone to dipotassium glycyrrhizinate is from 15:1 to 0.5:1. 8. Oral care composition according to any of the preceding claims, wherein the weight ratio of 4-hydroxyacetophenone to o-cimen-5-ol is from 10:1 to 0.5:1. 9. Oral care composition according to any of the preceding claims, for use in the treatment and/or prevention of dental plaque formation, caries formation, tartar formation, halitosis, gingivitis, periodontitis, peri-implant mucositis and/or peri-implantitis.